Dynamic Adaptations in the Human Low-Pressure Compartment Facilitating Cardiovascular Responses at Rest and Exercise

Abstract

The experimental description of the low-pressure cardiovascular compartment was developed from studies involving anesthetized whole animals. There are few studies in alert, conscious humans delineating the acute adaptations of the low-pressure compartment to maintain cardiovascular function and homeostasis in the variable demands of changing body positions and from rest to exercise. Available empirical data shows that the low-pressure compartment is effective at sequestering blood volume in response to medications and volume loading. Additionally, this unstressed blood volume can be mobilized acutely in situations of increased cardiac output such as exercise or mental stress. This mobilization during exercise is also associated with acute improvement of the low-pressure compartment conduit function (pulmonary and IVC conduit vessels). The unstressed volume mobilized from peripheral beds is also used to load the pulmonary vascular reservoir in addition to dilating low-pressure compartment conduit vessels. The low-pressure compartment is gravity and extramural pressure sensitive which leads to differences in cardiac filling capabilities in different body positions and body habitus. In this chapter we will review available data primarily in alert, conscious humans which provides insights to low-pressure compartment functioning at rest and at mental and physical stress.

1. Introduction

Despite the fact that low-pressure compartment experimental observations were dominant at the dawn of cardiovascular physiology and pathophysiologic experimentation, the field appears to have become quite dormant in terms of new studies and discoveries in recent years. This is not to say that the low-pressure compartment is any less important to overall cardiovascular homeostasis, which requires dynamic adaptations to facilitate major changes in cardiac output (CO) and venous return from moment to moment. We would also suggest that our understanding of the moment-to-moment hemodynamic adaptations within the cardiovascular system are not complete. These challenges have contributed to the difficulties of understanding diastolic function and overall acute manipulations of left ventricular (LV) loading conditions.

The low-pressure compartment is intimately involved in both right ventricular (RV) and LV loading, and until we have a scientifically clear understanding of these moment-to-moment hemodynamic adaptations in the intact, conscious human cardiovascular system, we will have an incomplete understanding of cardiac diastolic function and dysfunction. One might argue that the advent of molecular experimental techniques has displaced earlier mechanical circulatory approaches. It is our opinion that we have prematurely stopped investigating mechanical circulatory constructs in the integration of the low-pressure compartment into dynamic human physiology and pathophysiology. This has left us with a limited understanding of how rapid changes in CO are modulated by the low-pressure compartment, including rapid facilitatory changes in venous conduit and reservoir function.

In this chapter, we hope to provide an integrated view of the low-pressure compartment beyond vascular capacitance, focusing closely on interactions with cardiac reservoir and the conduit functions of the low-pressure compartment. Of necessity, we will promote a hypothetical framework using available empirical observations including our own.

The low-pressure cardiovascular compartment is comprised of systemic veins, ranging from venules up to conduit veins such as the inferior vena cava (IVC) and superior vena cava (SVC). When considering distribution of blood volume in terms of pressure compartments, approximately 80% of blood volume resides in the low-pressure system, with the rest located in the high-pressure system and in the chambers of the heart [1]. In states of hemodynamic equilibrium, 60–65% of total blood volume is located in the reservoir of the venous system [1, 2]. This blood is unstressed volume and is experiencing near zero transmural pressure [3]. Unstressed volume does not play a role in determining venous flow until it is recruited as stressed volume [4]. Stressed blood volume is the remaining blood volume (the difference of total blood volume and unstressed volume), and along with compliance, it affects venous pressure and cardiac output [2]. Vascular capacitance is a measure of the amount of blood present in a particular region of the cardiovascular system. The majority of this volume is in the veins and encompasses both stressed and unstressed volume [5]. Capacitance, stressed blood volume and unstressed blood volume are all dynamic aspects of the cardiovascular system and can increase or decrease from moment to moment.

1.1 Glossary of terms

Low-pressure cardiovascular compartment: This includes all elements of the systemic veins from venules up to conduit veins such as IVC and SVC.

Vascular capacitance: The ability of the blood vessels to sequester blood volume. This can be defined using pressure-volume relations with significant increase in blood volume in vessels with greater capacitance.

Unstressed blood volume: The amount of blood contained in regions of the vascular system that is exerting near-zero pressure on the venous system.

Stressed blood volume: The amount of blood that is actively exerting pressure in the venous system and affects venous flow and cardiac output.

Conduit veins: Veins which do not store blood (unstressed volume). They function to facilitate blood flow within the venous compartment. Examples are IVC, SVC, and pulmonary arteries.

Reservoir: Regions of the venous system that are capable of storing variable amounts of blood volume which respond acutely to hemodynamic changes, vasoactive drugs and neural stimulation. An example is the splanchnic venous reservoir which empties with exercise, but the pulmonary low-pressure vascular reservoir increases blood volume with exercise.

2. Vascular capacitance

Most scholars of cardiovascular physiology are aware of the ability of the low-pressure compartment to sequester and release stored blood volume. This has been demonstrated in our research and by prior investigators such as Clive Greenway and Carl Rothe. Greenway studied the splanchnic bed in cats and noted that it was able to sequester or pool 50–70% of the volume of blood that was either added (volume loading) or depleted (hemorrhaging) [6]. He also described the splanchnic system as a reservoir and detailed the shift from unstressed to stressed volume [2, 7]. Rothe reviewed how changes in vascular compliance and unstressed volume contribute to venous capacitance [3].

In a whole-animal model of acute left ventricular (LV) dysfunction leading to congestive heart failure (CHF), we demonstrated the capacity of the splanchnic low-pressure compartment to sequester increasing volumes of blood. This has been interpreted as mitigating central volume overload in cases of CHF. We, and others, have shown that this peripheral sequestration of blood volume can be translocated away from the periphery without a change in slope of the venous pressure volume relationship (an unstressed volume shift) [8, 9]. Our studies in fully anesthetized dogs suggested that compensation for volume loading is much more robust compared to compensation for hemorrhage or volume depletion [9].

In one of our animal studies, anesthetized dogs were used to determine how rapid volume loading and hemorrhaging affected the pressure-volume (P-V) relationship and CO [9]. Weight-based volume loading was performed by injecting IV fluid into the experimental dogs. The additional volume caused a large increase in intestinal blood volume (60 ± 6%) and cardiac output (178 ± 48%). Portal venous pressure increased by more than double from baseline. In some dogs, we simulated hemorrhaging by removing blood through venous catheters. This caused an initial decrease in intestinal blood volume to approximately 88% (p < 0.001) of the baseline value, cardiac output decreased to 52% (p < 0.005) and portal venous pressure decreased to approximately 3.2 mmHg (p < 0.01) from baseline of 5.8 mmHg. There was a parallel shift in the P-V relationship (Figure 1). It appeared that capacitance played a role in modulating CO, which remained relatively stable as we observed changes in blood volume. However, this stability persisted only until compensatory mechanisms of dilation and constriction were no longer effective.

Figure 1.

Top: an example from one dog showing changes in the intestinal pressure-volume relationship during volume loading and hemorrhage. Volume loading (filled-circle) shifted the relationship between portal venous pressure (P_pv) and intestinal blood volume (IBV) rightward from the control value (open-circle). The relationship gradually returned to the control position before hemorrhage (filled-triangle), which shifted the relationship leftward. Bottom: Group data from all 11 dogs studied. The numbers in parentheses indicate the approximate time after volume loading and after hemorrhage. Hemorrhage shifted the relationship leftward. Group data are presented. as mean ± SEM. Credit: this article was published in Ref. [9], copyright Elsevier (2002).

It is crucial to note that in this model during volume loading, the intestinal blood volume percentage increased from 100% (baseline volume) to approximately 140% while cardiac output remained relatively stable with only small changes (Figure 2). Our observations suggest that the splanchnic system serves as a reservoir for blood volume and is more effective at maintaining stable cardiac output during volume loading when intestinal blood volume increases. Conversely, during hemorrhage, when intestinal blood volume is depleted, this regulatory effect appears to be less pronounced. Figure 2 clearly shows that as unstressed volume increases up to its full extent (140% intestinal blood volume), there is no change in CO. This demonstrates effective sequestration of blood volume in the intestinal venous reservoir.

Figure 2.

Top: an example from one dog showing the relationship between cardiac output (CO) and intestinal blood volume (IBV) during volume loading and hemorrhage. Bottom: Group data from all 11 dogs studied. The relationships were fitted using cubic eqs. CO was relatively constant over a wide intermediate range of IBV. Credit: this article was published in Ref. [9], copyright Elsevier (2002).

We have extended these studies to alert, conscious humans involving administration of nitroglycerine demonstrating the increase in splanchnic sequestration of blood volume [10]. Blood-pool imaging, a sophisticated diagnostic technique, was employed to detect nuanced changes in regional blood volume. This measurement was subsequently interpreted as venous blood volume, providing valuable insights into the vascular dynamics of the study subjects. Human subjects, serving as the primary focus of our investigation, were subjected to a rigorous experimental protocol. They were randomly assigned to receive either sublingual nitroglycerin or an inert sugar pill. The administration of these substances was followed by a meticulous recording of data, both prior to and following their ingestion. This approach allowed for the precise quantification of the effects of nitroglycerin.

The results of the human studies were indeed remarkable. Following the sublingual administration of nitroglycerin, there was a noteworthy increase in splanchnic vascular capacity, amounting to 5.2 ± 6.9%. This change was found to be statistically significant with a p-value of less than 0.001. To visually represent this observed difference over time, please refer to Figure 3, which graphically illustrates the dynamic alterations in splanchnic vascular capacity for both the nitroglycerin group and the control group that received the placebo.

Figure 3.

Splanchnic vascular capacity changes at one-minute intervals before and after sublingual administration of 0.6 mg nitroglycerin (A) or sugar pills (B). Group values are presented as mean ± s.e.m.* p < 0.001; + = p < 0.05 vs. control measurements. Note: the average corrected count-rate during the five control measurements was considered to be 100% in the individual patient. The arrow indicates the time at which nitroglycerin or sugar pills were given. Credit: this research was originally published in Ref. [10].

Concurrently, in a parallel arm of our research, experimental canines were enlisted to create pressure-volume (P-V) curves. This approach allowed us to gain insights into the dynamics of the splanchnic vascular system under controlled conditions. In the canine subjects, mean arterial pressure (MAP) was precisely manipulated using angiotensin and nitroprusside, in addition to the administration of nitroglycerin.

Intriguingly, the outcomes in our canine experiments revealed distinct responses to these interventions. Angiotensin, a vasoconstrictor, induced a substantial 16% reduction in splanchnic vascular capacity (p < 0.001), highlighting the vasoconstrictive effects on the splanchnic circulation. Conversely, nitroprusside, a potent vasodilator, led to a remarkable 32% increase in splanchnic vascular capacity (p < 0.001), underscoring the profound impact of vasodilatory agents on splanchnic hemodynamics. Furthermore, the administration of nitroglycerin was found to induce a rightward shift in the P-V curve, indicative of the distinctive increase in unstressed volume created by this drug.

In sum, our study not only elucidates the methodology employed for assessing splanchnic vascular volume in humans, but also underscores the dynamic and multifaceted hemodynamic responses elicited by a diverse range of interventions. These interventions, encompassing both pharmacological agents and carefully controlled physiological manipulations, provide an understanding of the capabilities of the splanchnic vascular system.

Blood pool scintigraphy methods were also used in a novel study by Manyari et al. who investigated capacitance of the splanchnic region and assessed human P-V relationships [11]. Splanchnic vascular volume (SVV) was manipulated passively by using low levels of CPAP to change the subjects’ right atrial pressures. Healthy humans were recruited, and their red blood cells were labeled for radionuclide blood pool imaging. While in the supine position, scintigrams were captured to quantify SVV changes. To determine the baseline P-V relationship, patients were given increasing levels of CPAP from 0 to 12 cm H20 and SVV was recorded at each interval. Then, nitroglycerin was administered along with the increasing levels of CPAP and additional P-V curves were obtained. The same protocol was followed in a second group of subjects who were given a sugar pill instead of nitroglycerin.

In the control studies, there was a 7.4% increase in SVV when CPAP increased (from 0 to 12). This was a linear relationship (r = 0.74–0.98). After administration of nitroglycerin, SVV increased at each time interval with an increase of CPAP (2–6 minutes: 8.4% p < 0.001, 9–13 minutes: 9.4% p < 0.001, 20–24 minutes: 5.7% p < 0.01). The P-V curves of every patient in the nitroglycerin group experienced maximal displacement though a rightwards shift. Patients who received a sugar pill did not display any significant changes in the P-V curves. This study demonstrated, for the first time in humans, the increase in splanchnic unstressed venous volume via the venodilatory mechanism of sublingual nitroglycerin.

A more recent approach by Okamoto et al. using contemporary methods to investigate the effects of sublingual nitroglycerin on thoracic blood volume and splanchnic vascular capacitance yielded similar results [12]. Healthy patients were studied, and CPAP was used similarly to the study by Manyari [11]. After administration of nitroglycerin, there was a right-parallel shift in the splanchnic pressure-volume relationship (increased capacitance). Although the decrease in pulmonary blood after nitroglycerin was not statistically significant, the relative decrease in blood volume correlated with the increase in relative splanchnic volume (p = 0.01).

Splanchnic capacitance robustly increases with volume loading and seems to prevent increases in end diastolic pressure and CO. The response of splanchnic blood volume to hemorrhage, or dehydration, is less robust. Nitroglycerin is associated with the activation of splanchnic venodilation with increases in splanchnic unstressed volume. This effect of nitroglycerin is parallel to a decrease in pulmonary blood volume. The splanchnic bed is perhaps the largest and most hemodynamically significant capacitance bed in the human body.

Other medications like opiates have also demonstrated the ability to increase capacitance. Hsu’s study on morphine was conducted on subjects undergoing coronary artery bypass surgery [13]. Blood from the inferior and superior vena cava would normally drain by gravity into the reservoir used during the surgery. Increased capacitance was determined if there was a decrease in the amount of blood that flowed into this reservoir. The subjects were divided into 5 groups and received different dosages of morphine and/or a control solution. In all groups after morphine administration, capacitance increased by 8–15% of calculated blood volume (determined by a decrease in blood in the reservoir). The effects of morphine were suggested to be likely from both a neural and local effect.

Investigations of venous capacitance in the low-pressure compartment in alert, conscious humans are few and far between. We assessed forearm venous function in humans to determine how volume and pressure changes with mental stress [14]. Baseline forearm blood volume was assessed using radionuclide blood pool imaging. Vascular volume measurements were taken using occluding pressure (0, 10, 20, and 30 mmHg) to plot the V-P relationships (Figure 4). The subjects underwent mental stress by performing mathematical operations during the data collection. A 13.5% (p < 0.001) reduction in forearm unstressed volume with mental arithmetic stress was observed. Mental arithmetic stress also increased systolic and diastolic pressure (p < 0.001) and heart rate (p < 0.01). The linear relationship between volume and pressure was observed at baseline and, with a parallel shift, during mental arithmetic stress (Figure 5). This suggests that under these stressed conditions, blood volume moves away from the forearm possibly into the pulmonary reservoir component of the low-pressure compartment to provide for an increase in CO, which is known to increase in these conditions [15, 16, 17].

Figure 4.

Plots of individual patient data showing the regional forearm venous volume-pressure relations during control (o) and mental arithmetic stress (•) in 10 apparently normal subjects. Note that, despite interpatient variation in slope, the control and stress volume-pressure curves tend to be parallel in the same patient, and that in all patients a downward shift occurs during mental stress. Lines are drawn assuming linear volume-pressure relations with linear regression. Credit: Ref. [14].

Figure 5.

Plot of summary of group data showing the linear regressions of the forearm venous volume-pressure relation at control (C) and during mental arithmetic stress (MS) obtained by analysis of variance after testing revealed no lack of linearity or parallelism. At cuff pressures of 0- and 30-mmHg, the standard error of the estimate (SEE) was 1.52%; at 10- and 20-mmHg, 1.16%. Credit: Ref. [14].

3. The low-pressure compartment conduit function

Arthur Guyton pointed out that venous resistance is 19 times more important in determining cardiac output than arterial resistance. Most of the venous resistance resides in the IVC, which transmits two-thirds of CO at any point in time. Guyton used anesthetized whole animals to develop this hypothesis [18, 19]. Based on his research, more investigative work has been conducted in the field to investigate IVC conduit function in alert, conscious human subjects.

In our recent study, IVC dilation, measured by IVC cross sectional area (CSA), significantly increased in subjects during passive leg raise elevation and supine exercise [20]. Baseline images using non-contrasted CT were taken of the 14 healthy subjects in supine position. Next, images were taken when legs were passively elevated, returned to supine and during the exercise protocol. The participants exercised in the supine position on a cycling machine at 50% and 90% maximum effort. IVC CSA increased from baseline with passive leg raising (p < 0.001) and with 50% exercise (p < 0.05). This correlated with an increase in CO. See Figure 6 for the change in CO and VR. The increase in IVC CSA appeared to stabilize venous resistance (VR), as depicted by the unchanged venous resistance during supine passive leg raising or exercise. In this model, improvement in IVC caliber and decrease in VR appears to be passive as leg raising provided the same improvement in IVC dilation.

Figure 6.

Variation of cardiac output and VR with body position and exercise. The standard deviations for cardiac output (error bars) and venous resistance (numerical values) are shown. Note that VR is highest at rest and remains stable throughout all interventions including exercise. Credit: Ref. [20].

Goldhammer et al. noted that elite athletes have IVC remodeling with larger IVC CSA compared to the aorta, which points to remodeling of the IVC in response to repetitive exercise [21]. Swimmers have the largest degree of IVC remodeling. Goldhammer’s findings were confirmed in a later study by Hedman et al. [22] which examined the IVC in trained and untrained females. In the long-axis view of the IVC, the athletes measured 17% larger than the untrained females. The endurance athletes also had a larger IVC CSA compared to the untrained females. The above findings suggest a positive remodeling of the IVC conduit vein in athletes which would tend to reduce venous resistance during conditions of increased CO.

Support for venous remodeling is evident in our study of 14 healthy young individuals with varying BMI and levels of cardiovascular fitness (Figure 7) [20]. As BMI increases, there is an increase in aortic CSA, which would be the normal anthropometric expectation. However, venous CSA tends to decrease as BMI increases. This could be due to extramural pressure compressing the IVC in the supine position in obese individuals with increased extra abdominal fat. In our study, we also noted that individuals with higher BMI were also much less athletic, therefore, negative remodeling due to low cardiovascular fitness cannot be excluded as a cause for this decrease in IVC CSA with increasing BMI. In higher BMI individuals, ellipticity decreased as intra-IVC pressure increased with exercise [23]. Their IVC cross sections became circular as extramural pressure no longer defined IVC shape. These high BMI individuals still had smaller IVCs, thus IVC remodeling is more likely to be the explanation for smaller IVCs in higher BMI individuals (and vice versa).

Figure 7.

Correlation of IVC CSA (blue) and aortic CSA (red) with BMI at baseline. The difference between the two slopes was significant at p = 0.003. Credit: Ref. [20].

Preliminary data from our study on healthy, conscious humans demonstrates a negative effect of BMI on cardiac filling [23]. CT scans were used to measure IVC CSA of each subject at supine rest, legs elevated, and increasing increments of exercise. Subjects with a BMI below 25 were able to significantly increase e-wave velocity time integral (EVTI), a surrogate for CO, with increasing levels of supine exercise, whereas subjects with elevated BMI experienced increased IVC resistance and vascular resistance and were unable to increase EVTI. With each intervention, except for passive leg raising, there was a decrease in the IVC CSA in the elevated BMI group (p = 0.007). These findings suggest that the IVC may undergo negative remodeling in overweight, relatively unfit individuals.

Linicus conducted a study on vena cava compression in obese patients, revealing a strong correlation between a BMI exceeding 30 and an increased pressure gradient along the thoracic to abdominal vena cava (p = 0.0008) [24]. Variations in fat distribution patterns could account for the absence of elevated pressure in some higher BMI patients. Although this study did not measure IVC cross-sectional areas, it is reasonable to infer those patients with higher BMIs experienced more pronounced IVC compression. This necessitates an elevation in IVC pressure to maintain adequate blood flow, resulting in a greater pressure gradient between the IVC and the thoracic region.

We have also noted in alert, conscious humans, that IVC dilation in response to adenosine infusion produced an average of 63% increase IVC CSA [25]. After a 6-minute infusion of adenosine, there was a significant increase in IVC CSA, mitral inflow velocity and resting heart rate. The delta change of IVC CSA closely correlates with MVTVI (mitral valve time velocity integral) x HR (CO) in individual patients (Figure 8). The change in IVC CSA and MVTVI x HR from pre-infusion to during infusion was significant (r = 0.73, p = 0.006). Adenosine appears to improve preload through conduit IVC dilation with decreased venous resistance. Adenosine receptors located in either IVC smooth muscles or endothelium may contribute to IVC dilation [26].

Figure 8.

Regression lines for MVTVI x HR versus IVC CSA average. Δ IVC CSA average = IVC CSA average during infusion – IVC CSA average pre-infusion. Δ MVTVIXHR = MVTVIXHR during infusion - MVTVIXHR pre-infusion. Credit: Ref. [25].

This may be the explanation of presumed lusitropic effect alluded to by Nussbacher [27]. He observed that adenosine increased pulmonary capillary wedge pressure (PCWP), increased CO, and decreased arterial load (all p < 0.001). Adenosine did not reduce cardiac function in their subjects. The likely mechanism of the increased PCWP observed during adenosine infusion in humans is likely due to a lusitropic effect, mediated partially through IVC dilation in humans. This would occur through conduit vessel dilation (IVC and pulmonary) resulting in greater venous return with a lesser pressure drop from the periphery (lusitropic effect).

4. Low pressure compartment integration with cardiopulmonary circuit during exercise/increased cardiac output

During periods of exercise, cardiac output as well as cardiopulmonary blood volume increases. The source of the additional blood translocated to the cardiopulmonary system has been investigated by Flamm et al. [28]. In their study on redistribution of blood volume during upright exercise, images of acute blood volume changes in healthy, conscious subjects were taken by blood pool scans. These images depicted a shift in volume from the muscular and splanchnic beds to the cardiopulmonary circuit. During upright exercise, blood volume decreased in the legs (23%) and large decreases were seen in abdominal organs (spleen by 46%, kidney by 24% and liver by 18%). In contrast, thoracic blood volume increased (38%) and lung volume increased by 50%. During exercise, cardiac end diastolic volume increased by approximately 10%, suggesting that cardiac end diastolic loading is a part of the increased cardiac output response to exercise. The demonstration of blood volume translocation from the lower extremities and abdominal organs to the thoracic region during exercise illustrates the integral role that the splanchnic system has in modulating blood volume redistribution during periods of high demand. Flamm showed us that with acute upright exercise in humans, there is immediate release of peripheral venous blood into the central compartment.

In one study by Hopkins et al. [29], researchers hypothesized that athletes with the greatest pulmonary diffusion limitation for oxygen would have faster pulmonary transit times, and that increased pulmonary blood volume would allow for increased diffusion of oxygen. Healthy, male athletes were recruited, and baseline inert gas studied were performed. Cardiac output and first pass transit time were measured via radiocardiography by labeling a sample of blood in-vitro and injecting it back into the subject. This was performed again, one week later at maximal exercise effort. Mean pulmonary transit times during exercise significantly decreased from 9.32 ± 1.41 seconds at rest to less than 3 seconds during exercise (p < 0.001). Pulmonary blood volume significantly increased during exercise. These findings confirmed Flamm’s finding of blood translocating to the lungs. Hopkins et al. showed that this translocation of blood, centrally, is associated with concurrent acute improvement in pulmonary conduit vessel function resulting in decreased pulmonary transit time. There was also a correlation observed between pulmonary blood volume and diffusing capacity for oxygen (p < 0.001).

A recent proof-of-concept study by Monahan investigated the utility of echocardiography in measuring pulmonary transit time and found that 13 out of 14 healthy participants experienced a decrease in pulmonary transit time after exercise when compared to their baseline [30]. This study had several limitations including a small sample size (which did not include any obese patients or patients with cardiopulmonary disease), however it confirmed the expected decrease in pulmonary transit time after exercise. It also demonstrates the feasibility of the technique, which may become useful for assessing patients at the bedside.

It would appear that the capacitance bed is able to centrally translocate blood without major changes in its pressure volume relation (shifts in unstressed volume). Some of this central translocation moves to the venous conduit vessels to improve/stabilize venous resistance both in the pulmonary and systemic venous beds as noted by our study and by Hopkins [20, 29]. Goldhammer showed preliminary data which confirms that IVC remodeling is evident in athletes [21]. This system appears to operate passively after the positive remodeling has been completed to allow central translocation without increasing venous resistance. In the central compartment, actions requiring increased left ventricular loading such as upright exercise seem to be associated with an immediate loading of the central pulmonary blood reservoir with an increase of approximately 50% in pulmonary blood volume [28]. Other studies have confirmed that with exercise, pulmonary transit time is reduced suggesting that pulmonary conduit function acutely improves during times of increased cardiac output [28, 30]. These observations highlight the tight integration of the low-pressure compartment, capacitance, and conduit functions in adaptations to acute exercise.

5. Conclusions

We presented in this chapter an overview of the low-pressure compartment which considers both capacitance and conduit function of this compartment and how it is tightly integrated with acute hemodynamic changes within the cardiovascular system. A critical look at the available empirical data concerning the cardiovascular low-pressure compartment of the alert, conscious human suggests:

1. The low-pressure compartment is effective at sequestering blood volume in response to medications and volume loading.

2. This unstressed blood volume can be mobilized acutely in situations of increased cardiac output such as exercise.

3. This mobilization during exercise is associated with acute improvement of the low-pressure compartment conduit function (pulmonary and IVC conduit vessels).

4. Receptor induced improvement in conduit function has been demonstrated with adenosine infusion which dilates the IVC and increases PCWP via a lusitropic mechanism. It is unclear whether activation of adenosine receptors mediates the favorable conduit function associated with acute exercise.

5. The unstressed volume mobilized from peripheral beds during acute exercise is also used to load the pulmonary vascular reservoir, in addition to dilating low-pressure compartment conduit vessels. This pulmonary reservoir increase is 50% with acute upright exercise.

6. The low-pressure compartment is gravity and extramural pressure sensitive which leads to differences in cardiac filling capabilities in different body positions and body habitus.

The elegant mechanisms involving low-pressure compartment adaptations to acute changes in body position and cardiac output shows the ability of nature to create a system which uses remodeling and mainly passive changes to maintain cardiac diastolic function regardless of ambient conditions. These mechanisms are only now coming to clinical recognition and will require further detailed hemodynamic investigations to understand their full impact and enhance our ability to modulate these responses in health and disease.

Acknowledgments

We would like to acknowledge the Alberta Heritage Foundation for Medical Research (AHFMR) and the University of Calgary/Foothills Hospital for providing the means to allow VJBR to initiate experimental studies of the low-pressure compartment. Special thanks to JV Tyberg, MD, PhD (deceased) and Eldon Smith, MD who fostered a spirit of inquiry. We also thank Lauren Wright, B.S. for invaluable assistance in literature review.

Conflict of interest

The authors declare no conflict of interest.